title: Thioredoxin1 downregulates oxidized low-density lipoprotein-induced adhesion molecule expression via Smad3 protein.
abstract: Atherosclerosis is a chronic inflammation disease that is initiated by endothelial cell injury. Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. To understand whether thioredoxin1 (Trx1) participates in an antiinflammatory defense mechanism in atherosclerosis, we investigated the effect of Trx1 on the expression of two adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in human umbilical vein endothelial cells (HUVECs). Thioredoxin1 and dominant-negative mutant thioredoxin1 (TD) were transiently overexpressed using adenovirus vector gene transfer. Our data showed that Trx1 overexpression suppressed ox-LDL-induced adhesion molecule expression in HUVECs. The overexpression of Trx1 promoted ox-LDL-induced Smad3 phosphorylation and nuclear translocation. A co-immunoprecipitation assay indicated that Smad3 continued to interact with Trx1 with or without ox-LDL stimulation. These results suggest that Trx1 inherently suppresses VCAM-1 and ICAM-1 expression in vascular endothelia and may prevent the initiation of atherosclerosis by attenuating adhesion molecule expression. The enhancement of Smad3 phosphorylation and nuclear expression appears to be primarily responsible for the Trx1-induced downregulation of adhesion molecules.
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics & Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Beidong
authors.initials: B
authors.lastname: Chen
authors.forename: Wendong
authors.initials: W
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Ruomei
authors.initials: R
authors.lastname: Qi
mesh_terms: D000256:Adenoviridae; D000704:Analysis of Variance; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C491203:TXN protein, human; C099252:oxidized low density lipoprotein; D013879:Thioredoxins